Synthesis and biological activity of thiophene bioisosteres of natural styryl lactone goniofufurone and related compounds.

Ten new thiophene derivatives related to goniofufurone have been obtained by multistep synthesis starting from d-glucose. The critical step of the synthesis was the Grignard reaction of 2-thienyl magnesium bromide with a protected dialdose, yielding the C-5 epimeric thiophene derivatives 9 and 10. The mixture was oxidized to the 5-keto derivative 11, which after deprotection was converted to the corresponding keto-lactone 14.

Quality of life following two different techniques of an open ventral hernia repair for large hernias: a prospective randomized study.

Background: We compare the health-related quality of life (QoL) of patients with incision hernias before and after surgery with two different techniques.

Methods: In this prospective randomized study, the study population consisted of all patients who underwent the first surgical incisional hernias repair during the 1-year study period. Patients who met the criteria for inclusion in the study were randomized into two groups: the first group consisted of patients operated by an open Rives sublay technique, and the second group included patients operated by a segregation component technique.

Structure based design, synthesis and in vitro antitumour activity of tiazofurin stereoisomers with nitrogen functions at the C-2' or C-3' positions.

Three novel tiazofurin analogues having d-arabino stereochemistry and nitrogen functionalities at the C-2' position (5-7) have been designed and synthesized in multistep sequences, starting from d-glucose. The known d-xylo stereoisomer of 1 (compound 2) along with two new analogues bearing nitrogen functions at the C-3' (3 and 4) has also been synthesized from the same sugar precursor. The synthetic sequence consisted of the following three stages: (i) the multistep synthesis of suitably protected pentofuranosyl cyanides, (ii) the construction of ethyl thiazole-4-carboxylate part by cyclocondensation of thus obtained glycofuranosyl cyanides with l-cysteine ethyl ester followed by dehydrogenation, and (iii) the final transformation of the ethyl thiazole-4-carboxylates into the target tiazofurin analogues using the esters ammonolysis.

Anticancer activity of novel steroidal 6-substituted 4-en-3-one D-seco dinitriles.

Steroidal 16,17-seco-16,17a-dinitriles possessing 4-ene-3,6-dione (3), 6-methylene-4-en-3-one (5), (6E)-hydroxyimino-4-en-3β-ol (9) or (6E)-hydroxyimino-4-en-3-one (10) moiety were synthesized starting from 3β-acetoxy-16,17-secoandrost-4-ene-16,17a-dinitrile (1). Antiproliferative activity of the newly synthesized compounds, as well as previously synthesized 3-oxo-16,17-secoandrosta-1,4-diene-16,17a-dinitrile (VII), was tested in vitro. Compound 9 displayed submicromolar antiproliferative activity against human cervical carcinoma (HeLa) cells (IC 0.

Design, synthesis and in vitro antitumour activity of new goniofufurone and 7-epi-goniofufurone mimics with halogen or azido groups at the C-7 position.

A series of new antitumour lactones containing the [3.3.0] bicyclic furano-lactone core and the halogen or azido group at the C-7 position have been designed, synthesized, and evaluated for their in vitro antitumour activity against a panel of human tumour cell lines.

Synthesis and in vitro antitumour activity of tiazofurin analogues with nitrogen functionalities at the C-2' position.

Synthesis of three tiazofurin (1) isosteres with nitrogen functionalities at the C-2' position (N3, NH2 and NH3(+)Cl(-)) has been achieved, in multistep sequences, starting from monoacetone d-glucose. A number of potential bioisosteres of 1 bearing acylamido functions at the C-2' position have also been synthesized from the same sugar precursor. In vitro cytotoxicities of target molecules against a number of human tumour cell lines were recorded and compared with those observed for lead molecule 1.

Androstane derivatives induce apoptotic death in MDA-MB-231 breast cancer cells.

Biological investigation was conducted to study in vitro antiproliferative and pro-apoptotic potential of selected 17α-picolyl and 17(E)-picolinylidene androstane derivatives. The antiproliferative impact was examined on six human tumor cell lines, including two types of breast (MCF-7 and MDA-MB-231), prostate (PC3), cervical (HeLa), colon (HT 29) and lung cancer (A549), as well as one normal fetal lung fibroblasts cell line (MRC-5). All derivatives selectively decreased proliferation of estrogen receptor negative MDA-MB-231 breast cancer cells after 48 h and 72 h treatment and compounds showed time-dependent activity.

Synthesis, structural analysis and antitumor activity of novel 17α-picolyl and 17(E)-picolinylidene A-modified androstane derivatives.

The heterocyclic ring at C-17 position of the androstane compounds plays an important role in biological activity. The aim of the present study was to synthesize and evaluate potential antitumor activity of different A-modified 17α-picolyl and 17(E)-picolinylidene androstane derivatives. In several synthetic steps, novel derivatives bearing the hydroximino, nitrile or lactame functions in A-ring were synthesized and characterized according to the spectral data, by mass analysis as well as XRD analysis (compounds 6, 13 and 15).